The bottom line is that these two groups have produced a commonsense, evidence-based manifesto that guides clinicians to provide the correct treatment of advanced bladder cancer, based on evidence rather than rhetoric and hype.

— Derek Raghavan, MD, PhD, FACP, FRACP, FASCO

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I like economies of scale, and thus it makes perfect sense that ASCO has set a formal process to allow potential endorsement of selected guidelines from other organizations, rather than redoing the whole process. Recently, we have seen the publication of a formal endorsement of the European Association of Urology (EAU) guidance on management of advanced bladder cancer¹ by an ASCO committee convened for that specific purpose.² The ASCO-endorsed recommendations are summarized in this issue of The ASCO Post.

In brief, the ASCO committee emphasized the importance of multidisciplinary input in management planning, with the necessity of referral to a medical oncologist and radiation oncologist for discussion of neoadjuvant chemotherapy and bladder preservation, respectively, as an addition to the EAU document. ASCO endorsed the key role for cisplatin-based neoadjuvant chemotherapy prior to radical cystectomy for otherwise healthy patients with invasive bladder cancer. Added important recommendations included radical cystectomy as treatment of choice for healthy patients with T2–4a, N0 M0 bladder cancer, chemoradiation-based bladder preservation for less-robust patients or those declining surgery, and cisplatin-based regimens (gemcitabine-cisplatin, MVAC [methotrexate, vinblastine, doxorubicin, and cisplatin] or dose-dense MVAC) for metastatic disease. In the setting of relapse after platinum therapy, either entry into a clinical trial or single-agent salvage chemotherapy was recommended. The ASCO committee modified the EAU recommendation against non–platinum-containing neoadjuvant chemotherapy by suggesting it may have a role if the goal is surgical downstaging; I’m not really sure what level 1 data support that view, but I guess it is reasonable as a broad concept.

The Role of Adjuvant Chemotherapy

Fortunately, both committees avoided the temptation to commit the rookie mistake of overinterpreting the many underpowered adjuvant trials, which have been methodologically flawed.³ Sternberg and colleagues⁴ in the European Organization for Research and Treatment of Cancer (EORTC) and Intergroup attempted to resolve the question about the role of adjuvant cisplatin-based chemotherapy after radical cystectomy but closed the study prematurely due to lack of accrual. They did secure participation from 284 of the planned 660 patients and were able to demonstrate a disease-free survival benefit but only a weak trend in favor of adjuvant chemotherapy for overall survival. Surprisingly, the group that benefited most comprised patients who had node-negative disease, calling into question whether the chemotherapy compensated for suboptimal surgery. Another potential explanation might have been that four cycles of adjuvant chemotherapy simply was not enough, although this seems unlikely to me. An Italian randomized trial of adjuvant gemcitabine/cisplatin had actually shown inferior survival!⁵

I was thus pleased to see that both committees acknowledged the existence of adjuvant chemotherapy, noting that it could be given to patients with high-risk, invasive disease after cystectomy but without making any false promises. Fortunately, they avoided the unwise temptations offered by propensity-matched (potentially biased) retrospective nonrandomized “real experience” series.

Remarkable Consensus

I looked carefully to see where ASCO and EAU did not share a common view. In fact, there was remarkable consensus, apart from relatively minor wordsmithing, for the major issues except the role of radiation therapy. The ASCO committee reviewed the available data and concluded, in contrast to EAU, that there is no role for radiotherapy in the management of primary bladder cancer, unless it is in the context of chemoradiation for bladder preservation. Frankly, I completely agree with the ASCO stance, although I would comment that occasionally a palliative dose of radiation to the bladder and surrounds will reduce some of the symptoms of local recurrence.

The bottom line is that these two groups have produced a commonsense, evidence-based manifesto that guides clinicians to provide the correct treatment of advanced bladder cancer, based on evidence rather than rhetoric and hype. ■

Disclosure: Dr. Raghavan reported no potential conflicts of interest.

References

1. Witjes JA, Compérat E, Cowan NC, et al: EAU guidelines on muscle-invasive and metastatic bladder cancer: Summary of the 2013 guidelines. Eur Urol 65:778-792, 2014.

2. Milowsky MI, Rumble RB, Booth CM, et al: Guideline on muscle-invasive and metastatic bladder cancer (European Association of Urology guideline): American Society of Clinical Oncology clinical practice guideline endorsement. J Clin Oncol. March 21, 2016 (early release online).

3. Raghavan D, Bawtinhimer A, Mahoney J, et al: Adjuvant chemotherapy for bladder cancer—Why does level 1 evidence not support it? Ann Oncol 25:1930-1934, 2014.

4. Sternberg CN, Skoneczna I, Kerst JM et al: Immediate versus deferred chemotherapy after radical cystectomy in patients with pT3-pT4 or N+ M0 urothelial carcinoma of the bladder (EORTC 30994): An intergroup, open-label randomised phase 3 trial. Lancet Oncol 16:76-86, 2015.

5. Cognetti F, Ruggeri EM, Felici A, et al: Adjuvant chemotherapy with cisplatin and gemcitabine versus chemotherapy at relapse in patients with muscle-invasive bladder cancer submitted to radical cystectomy: An Italian, multicenter, randomized phase III trial. Ann Oncol 23:695-700, 2012.